Abstract:

Objective To investigate the effect of liraglutide combined with zinc alpha2 glycoprotein （ZAG）on palmitic acid⁃induced HepG2 cell apoptosis，lipid metabolism and the expression of inflammatory factor. Methods Real⁃time quantitative PCR（RT⁃qPCR）and western blotting were used to analyze the expression levels of ZAG in liver tissues of patients with non⁃alcoholic fatty liver disease（NALFD）and palmitic acid⁃induced HepG2 cells. HepG2 cells were divided into control group，palmitic acid group，palmitic acid + liraglutide group，palmitic acid + pcDNA⁃ZAG group，palmitic acid + liraglutide + ZAG shRNA group，palmitic acid + liraglutide + pcDNA⁃ ZAG group. Cell apoptosis was detected by flow cytometry. Kit was applied to determine the levels of total cholesterol （TC）and triglycerides（TG）in the cells，as well as the levels of interleukin 6（IL⁃6）and tumor necrosis factor⁃α （TNF⁃α）in the supernatant of the cell culture medium. Results The expression of ZAG mRNA and ZAG protein in liver tissues of NALFD patients was significantly reduced（P < 0.05）. Treatment with Palmitic acid significantly down⁃regulated the expression of ZAG mRNA and ZAG protein，increased the levels of TC，TG，IL⁃6 and TNF⁃α， and increased the apoptosis rate of HepG2 cells（P < 0.05）. Treatment with liraglutide or over⁃expression of pcDNA⁃ ZAG significantly inhibited palmitic acid⁃induced apoptosis of HepG2 cells，and reduced the levels of TC，TG，IL⁃6 and TNF ⁃α（P < 0.05）. Silencing ZAG significantly weakened the effect of liraglutide on palmitic acid ⁃induced apoptosis，TC，TG，IL ⁃6 and TNF ⁃ α levels in HepG2 cells（P < 0.05）. Over ⁃ expression of ZAG significantly enhanced the effect of liraglutide on palmitic acid⁃induced apoptosis，TC，TG，IL⁃6 and TNF⁃α levels in HepG2 cells（P < 0.05）. Conclusion Liraglutide combined with ZAG can inhibit palmitic acid⁃induced apoptosis，lipid deposition and inflammatory reaction in HepG2 cells. 

Key words:

liraglutide, zinc alpha2 glycoprotein, palmitic acid, HepG2 cells, apoptosis, inflamMolation, triglycerides